Can Epigenetics Explain Homosexuality?

Scientists propose a new model for how homosexuality develops, but observers say it will be difficult to test.

By Sabrina Richards | January 1, 2013

WIKIMEDIA, theodoranian.Researchers looking for a genetic signature of homosexuality have been barking up the wrong tree, according to a trio of researchers in the United States and Sweden. Instead, the scientists posit, epigenetic influences acting on androgen signaling in the brain may underlie sexual orientation. In a paper published last week (December 11) in The Quarterly Review of Biology, they propose a model describing how epigenetic markers that steer sexual development in males could promote homosexual orientation in females, and vice versa. The scientists offer their model to explain both the tendency of homosexuality to run in families, and the fact that so far no “homosexual gene” has been identified.

“It’s a very provocative, very interesting new twist that is plausible,” said Margaret McCarthy, a neuroscientist at the University of Maryland who studies how hormones influence brain development and was not involved in producing the model. But, she cautioned, so far the theory “is not supported by any data.”

Indeed, Andrea Ciani, an evolutionary psychologist at the University of Padova, thinks that a variety of factors, including genes and epigenetics, influence sexual orientation. “It’s a little bit vain to think we’ll find the answer to homosexuality as a whole.”

The model was developed by William Rice, an evolutionary geneticist at the University of California, Santa Barbara; Sergey Gavrilets, a mathematician at the University of Tennessee; and Urban Friberg, an evolutionary biologist at the University of Uppsala. The notion that epigenetics, rather than genetics, is the primary force promoting homosexuality sprang from several observations, explained Rice.

First, evidence shows that homosexuality can run in families. Still, only 20 percent of identical twins are both gay, said Rice. Furthermore, linkage studies looking for a genetic underpinning to sexual orientation have not turned up any “major” homosexual genes, Rice noted. “This made us suspicious that something besides genes produces heritability that isn’t genetic.” Epigenetics fits the bill.

The model focuses on the role of epigenetics in shaping how cells respond to androgen signaling, an important determinant of gonad development. The researchers suggest that androgens are also important factors in molding sexual orientation, and that various genes involved in mediating androgen signaling are regulated by epigenetic modifications. These epigenetic marks, they argue, can be passed on between generations.

As an example of how androgens shape sexuality, the researchers point to girls with congenital adrenal hyperplasia (CAH), who produce very high levels of testosterone and often display masculinized genitalia and higher rates of same-sex attraction. But testosterone levels are sometimes the same in normally developing male and female fetuses—without masculinizing the females—suggesting that something else must be playing a role.

The answer, they hypothesized, has to do with sensitivity to androgens. There are a variety of proteins that can modify androgen signaling, and the researchers hypothesize that differences in sensitivity to these signals between male and female fetuses help mediate their sexual differentiation. Rice and his colleagues suggest that such sensitivity may be regulated by the acquisition of epigenetic marks that make girls less sensitive to masculinizing androgens, or make boys more sensitive.

Such epi-marks are typically accrued early in development, as cells are programmed to become specific adult cell types. But, the researchers speculate, perhaps they could be inherited from a parent. Most epigenetic modifications are erased during development of germ cells and soon after fertilization so that cell lineages can be programmed with new epigenetic modifications. But if epi-marks that direct sexual development are not erased correctly, a mother could pass down epi-marks that direct female development to her son, resulting in an attraction to men, and vice versa for a father and his daughters, the researchers theorize.

They also expect that specific epi-marks will regulate sensitivity differently in the brain versus gonads, resulting in same-sex attraction even when normal genital development occurs, said Gavrilets.

Eric Vilain, a neuroscientist at the University of California, Los Angeles, worries that the model, which “might be true,” makes a few simplistic generalizations. “It assumes the same mechanism [for development of sexual orientation] in both sexes . . . and that androgen levels play an important role in the development of sexual orientation”—neither of which has been demonstrated, he said.

Though girls with CAH do show higher rates of homosexual orientation, their exposure to testosterone “is so high it actually masculinizes their genitalia,” said Vilain, who researches mammalian sexual development. “It remains to be seen whether smaller variants of testosterone that do not result [in masculinized genitalia] also lead to attraction of same sex partners.”

In addition, the model’s predictions may be difficult to examine. Determining whether epi-marks have not been erased will be difficult to test, said Vilain, because the marks relevant to sexual orientation will probably be in the brain. But Rice proposes that because homosexuality can run in families, surveying the epigenomes of sperm from men with or without lesbian daughters could reveal key differences.

Fascinating as it may be to understand the biological basis of sexual orientation, however, not everyone is convinced it’s a necessary line of investigation. “Should we test this? Is it important for us to know?” asked McCarthy. “Homosexuality is not a disease, it’s part of natural human variation. I’m not sure there’s a good reason to delve this deeply into it. I think we’ve reached the point that we have enough evidence that there’s a biological basis for sexual orientation.” It would be more helpful to people to get a better handle on the epigenetics of cancer or mental illness, she added.

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Genetics (or epigenetics) is one of the most popular 'devil made me do it so it's OK' theories in recent years. What is most interesting is just why this theory, but not the testing of this theory, is so popular. What has happened is that it has become 'politically correct.' This is cultural change. The body has basic mechanisms that provide biochemical rewards for sexual conduct, and there are a lot of methods that can be used to evoke these mechanisms and secure those rewards. This is separate from social mechanisms related to empathy and manipulation in human groups, most of which have always been same-sex since most human interactions in 'primitive' societies appear to be same-sex and related to manipulation of status and social alliances. Sex could be used into the context of these social interactions. For example, in ancient Greece, sex between males was often an important part of male culture, and I'm sure that a genetic change was not behindt his.

Although suggesting that epigenetics is causal does bring a needed change of focus from the determinlistic "gene" perspective, it cannot of itself resolve the mystery. The source of change is likely wrapped deeply in subtle variations of development at, perhaps, multiple junctures.

Of course epigentic change will be found and duly tallied, but the question is Which of such changes indicate causality (or precursory early indicators of change) and which result from the convoluted cascade(s) of minutely skewed developmental events? Good luck in parsing that data.

A more productive research program might be to follow interactions between the predisposed immune system of mother and that of the developing prenate, as earlier studies suggest. Still, one might expect that only an integrated spectrum of data types from serum taken over the course of gestation will offer suggestive signals.

Perhaps while you're at it you might work up some autism (ASD) data as well.

On page 210 of his book: Gay Straight and the Reasons why, LeVay discusses my model for the development of heterosexual and homosexual preferences: “This model is attractive in that it solves the “binding problem” of sexual attraction. By that I mean the problem of why all the different features of men or women (visual appearance and feel of face, body, and genitals; voice quality, smell; personality and behavior, etc.) attract people as a more or less coherent package representing one sex, rather than as an arbitrary collage of male and female characteristics. If all these characteristics come to be attractive because they were experienced in association with a male- or female-specific pheromone, then they will naturally go together even in the absence of complex genetically coded instructions.”
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We now know considerable more about the complexity of genetically coded instructions — enough to say that what is known is insufficient in attempts to explain anything about the adaptive evolution of sexual preferences.

LeVay adds that “Still, even in fruit flies, other sensory input besides pheromones — acoustic, tactile, and visual stimuli — play a role in sexual attraction, and sex specific responses to these stimuli appear to be innate rather than learned by association [36.]. We simply don’t know where the boundary between prespecified attraction and learned association lie in our own species, nor do we have compelling evidence for the primacy of one sense over another.”
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Neuroscientists have known for many years precisely where the boundary lies between genetically predisposed attraction and learned associations in species from microbes to man. The most compelling evidence available shows that the epigenetic effects of olfactory/pheromonal input clearly establish olfaction as the primary sense and that it is responsible for adaptive evolution via ecological, social, neurogenic, and socio-cognitive niche construction across the evolutionary continuum that includes differences in sexual orientation.

As an alternative read the 57-page journal article concurrently published as a book chapter (that LeVay discussed in the context of my model): The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences

I am not a trained biologist, so I remain agnostic on the question of the "causes" of homosexuality.

I am, however, concerned by the criticisms of Rice et al, offered by Mccarthy and Vilain. If correctly reported, they seem to discount the new model because it lacks empirical verification. On the other hand, the last time I looked, scientists tended to generate hypotheses and then subject them to rigorous testing. The contribution if Rice et al. seems to qualify as a hypthetical model awaiting testing (however difficult that might be). So, surely the criticism is at best premature.

More unsettling is Ciani's comment that Rice et al. are "a little bit vain" because their model purports to explain so much with so little. Apart from any possible connection to the "Gordian knot," I wonder about the idea that scientists might be vain. What a shock! But what does this have to do with whether or not these arrogant creatures have actaully figured something out?

I am not a trained biologist, so I remain agnostic on the question of the "causes" of homosexuality.

I am, however, concerned by the criticisms of Rice et al, offered by McCarthy and Vilain. If correctly reported, they seem to discount the new model because it lacks empirical verification. On the other hand, the last time I looked, scientists tended to generate hypotheses and then subject them to rigorous testing. The contribution of Rice et al. seems to qualify as a hypothetical model awaiting testing (however difficult that might be). So, surely the criticism is premature.

More unsettling is Ciani's comment that Rice et al. are "a little bit vain" because their model purports to explain so much with so little. Apart from any possible connection to the "Gordian knot," I wonder about the idea that scientists might be vain. What a shock! But what does this have to do with whether or not these allegedly arrogant creatures have actually figured something out?

Rice et al (2012) with my emphasis: "All of the steps in Figure 2 could also be influenced by sex-specific regulation of miRNA levels that are known to influence sexually dimorphism of mRNA concentrations in the brains of mice, and to be influenced by epigenetic control that is heritable across at least one generation (Morgan and Bale 2011)."

Others may hear more about the miRNA / mRNA balance, which I included in the notes that detail the diagram of my model linked below (click twice or cut and paste if it does not lead to the F1000 poster).

“Homosexuality is not a disease, it’s part of natural human variation."

It is caused by man , as an obligate herbivorefrugivore , eating meat. This leads to increased iron which leads to increased oxidation of the DNA and increased reproduction of epigenetic markers (increasing the number of cells with faults) and the result , homosexuality as well as all other genetic diseases. Iron causing the increase in faults is evidenced in this study , iron leads to bowel cancer by increasing the number of cells with faults.

"Iron could be raising the risk of bowel cancer by increasing the number of cells in the bowel with APC faults."

I am convinced that with the current evidence showing trans-sexualizing of certain fish species from run-off of birth control chemicals that these substances have much to do with the etiology of homosexual tendency from residual effects in those who have used them and from the environmental pollution they have caused. Since evidence shows that estrogen plays a role in masculinization during certain stages of gestation, it would be no surprise that these chemicals, most properly called Zeno-estrogens could influence the masculinization of especially the male fetus and possibly have an effect on the femals fetus also. Since these compounds can be horrifically stable and can essentially wipe our the sites to which they are attached causing potential re-cycling of them in the organism, the possibility of these altering the sexual development of the fetus is a quite plausible possibility. Since the number of these sites is quite variable inter-individually, presumably affected by genetic variation, it could explain at least in part the high co-incedence of homosexuality among identical twins and in families. The same thing can explain why auto-immune disorders have a quasi-genetic incedence. Suppose, for instance that exposure to a common cold pathogen produces an antibody that is direct for the antigen but mildly cross-reacts with a particular varient of a protein in some individuals. The possibility of an auto-immune disorder developing increases. The same line of reasoning can be used to explain apparrently genetic, or, quasi-genetic origins of homosexual tendency.

Such a theory needs to be well thought out and investigated, But I do not think it will be as it cuts into the holy grail of birth control, which although it was specifically developed for the eugenic puropose of mass murder (the inventor if " the pill" was on the Nazi commission responsible for mass-eugenic murder) and was employed with the full intent of exterminating many peoples such as was attempted in Puerto Rico, and inspite of the fact that it is directly causal of behaviors that have put women at an extremely high lifetime exposure risk for HPV, chalamydia, HPV and a host of other venereal diseases and treatment resistent varients. Also, the possibility of a huge class-action suit against the holy grail of Planned Parenthood and drug companies for their role in negligently exposing for profit so many to the difficulties associated with homosexual tendency would be economically cripling.

to say there is no reason to research this so deeply is ridiculous. considering the animosity toward gender differences, it is important to release these people from the long standing and incorrect stigma of poor moral decisions and everything that entails. religious groups especially villify these people, who certainly do NOT choose to be this way but are following what their mind and body are telling them is the right thing to do. vindication is justified here just as much as it was for blacks or any other group that were broadly classified as deviant and wrong.

I find the tone of this article interesting. Ciani talks about finding the "answer to homosexuality." Perhaps it's just a translation problem; the answer to that would be perhaps more careful editing. My own feeling is that perhaps McCarthy raises an issue that needs to be discussed. Are there other behaviors we need to examine for causality?

Just as plausible of a hypothesis is that homosexuality is seen in families (if it actually is) due to a lack of nurturing (bad parenting if you will) passed from generation to generation. Epigenetics is influenced by behavior. http://en.wikipedia.org/wiki/Behavioral_epigenetics for a primer. So this could all occur post-utero and, thus, evolution has not eradicated homosexuality because it has nothing to do with inheritance of genetic material per se.

Sadly the liberal agenda makes positing this hypothesis impossible because any scientist who propoosed it would be fired from any research position at a university and likely any grant money would be removed because of promoting discrimination. Can you see the federal government denying grant money because a scientist wanted to prove this hypothesis? I can.

I bet the truth is that homosexuality is just a choice as most of us have always figured and not any sort of immutable characteristic. Sadly, the liberal agenda has stripped our society of our freedoms of speech and religion. If a scientist proposed this idea he would face retaliation despite the fact that nothing makes this hypothesis less plausible. This is no longer about seeking the truth but stuffing an agenda down the throats of Americans.

The media does NOTHING to correct the constant comparison of homosexuality (not genetic despite many years of trying to find a genetic link) and race (clearly this one is genetic)! The liberal machine might, and pretty much has, won but the fallout in the abrogation of the rights of citizens to speak freely and practice their religious beliefs without fear of retaliation will last for generations. I live in FEAR of expressing a contrary opinion to something that is fairly debatable.

A travesty of justice to allow the courts to force acceptance of homosexuality onto American society by judicial fiat. There is only the suppression of the truth.

I am not saying that society cannot choose to treat homosexuality as acceptable behavior - I am saying that the gutting of our constitutional rights to speech and religion to force this onto American society is not a just way to accomplish this.

Which constitutional rights are being gutted exactly? There is a highly lucrative cable TV channel dedicated specifically to battling the "liberal agenda." Are you sure your rights are being trampled, or do you just not like the direction you see us heading?